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Journal of Antimicrobial Chemotherapy (1996) 38, 1-3
Leading article
to human health: (i) antibiotic-resistant bacteria pathogenic to humans are selected, the
foodstuff is contaminated during slaughter
and/or food preparation, the food is ingested,
the bacteria cause an infection that requires
J Antimicrob Chemother 1996; 38: 1-3
antibiotic treatment and therapy is comproAntibiotic resistance is often an emotive and mised; (ii) antibiotic-resistant bacteria noncontroversial issue, and the potential role of the pathogenic to humans are selected in the
use of antibiotics in veterinary medicine and animal, the foodstuff is contaminated and
animal husbandry and the implications of the ingested, and the bacteria transfer the resisttransfer of antibiotic-resistant bacteria to man, ance to other bacteria in the human gut; (iii)
subsequent infection and treatment is one of antibiotics remain as residues in animal
the areas most frequently discussed, but little products, which allows the selection of
researched. This article attempts to put the antibiotic-resistant bacteria in the consumer of
currently available information into perspec- the food.
tive.
In addition, it has recently been demonBacterial resistance to antimicrobial agents strated that DNA encoding antibiotic-resistcan be encoded on the chromosome or on a ance genes can contaminate naturally
transmissable element such as a plasmid occurring or semi-synthetic antibiotic prep(Datta, 1984). Chromosomal resistance is arations; if such DNA could be incorporated
transferred only to daughter progeny, whereas and expressed by pathogenic bacteria
plasmid mediated resistance can be transferred in an animal or human gut this would
to other species of bacteria. It has been well provide another route for the selection and
established that the hospital environment transfer of antibiotic resistance (Webb &
contains a large reservoir of bacteria, and that Davies, 1993).
nosocomial infections caused by EnterobacteriAntibiotics are used in animals both to treat
aceae such as Serratia marcescens, or skin infections and as growth promotors, and so
commensals such as Staphylococcus aureus are antibiotic-resistant strains can emerge both in
a major problem. The widespread use of healthy and sick animals. There is clear
antimicrobial agents in human medicine has evidence to show that with an increase in the
encouraged the emergence of antibiotic-resist- consumption of antibiotics by animals there
ant bacteria during therapy, plasmid-mediated has been a similar rise in the number of
mechanisms of resistance to be maintained and antibiotic-resistant strains isolated (Levy,
transferred within the hospital environment, Burke & Wallace, 1987). Although there is
and antibiotic-resistant bacteria to become part some dispute as to the absolute definition of a
of the commensal flora of healthy individuals true zoonosis, the species of bacteria that cause
(Saunders, 1981). Sensible antibiotic prescrib- zoonoses over which most public concern is
ing and good hospital infection control expressed are those that cause diarrhoeal
procedures are the only sure methods for diseases (Campylobacter spp., Salmonella
reducing the level of antibiotic resistance in serotypes, etc). The bacterial species that infect
institutions.
those that work in close proximity with
The intestinal flora of animals can provide animals, such as farmers, veterinary surgeons
another reservoir of antibiotic-resistant bac- and slaughterhouse workers, present little risk
teria; such strains are most frequently found in to the human population in general. In 1976
animals that are intensively farmed, such as Levy, Fitzgerald & Macone, demonstrated that
poultry, calves and pigs (Linton, 1977, 1986). plasmids encoding resistance to antibiotics
There are three possible routes by which the used in man could be transfered from chicken
use of antibiotics in animals could pose a risk to chicken, and from chicken to man. One year
Does the use of antimicrobial agents in
veterinary medicine and animal husbandry select
antibiotic-resistant bacteria that infect man and
compromise antimicrobial chemotherapy?
0305-7453/96/070001 +03 $12.00/0
f, 1996 The British Society for Antimicrobial Chemotherapy
Leading article
later, Linton (1977) showed that antibiotic-resistant Escherichia colt could be transferred
from poultry to a food-handler's hands during
food preparation. The transmision of enteric
bacteria to consumers via this route has
undoubtedly been established, and prevention
of food poisoning is the basis of food hygiene
and Public Health regulations in many
countries. However, only for salmonellae has
the pathway of transfer of antibiotic-resistant
bacteria from animals to foodstuffs to man and
subsequent infection been clearly demonstrated
(Lyons el al., 1980; Bezanson, Khakhria &
Bollegraaf, 1983; Holmberg el al., 1984, Mishu
el al., 1991). There have also been several
reports suggesting the transfer of antibiotic-resistant bacteria from animals to man including
chloramphenicol-resistant Salmonella newport
(Spika el al., 1987), quinolone-resistant
Campvlobacter spp. (Endtz el al., 1991) and
chloramphenicol-resistant Yersinia enierocoliiica (Perez-Trallero el al., 1988). However, clear
evidence showing beyond doubt that antibiotic-resistant bacteria arising in animals
cause subsequent infection in man which is
then difficult to treat are difficult to find.
Furthermore a drug to which the organism is
resistant may not be a therapeutic drug of
choice for man. However, this is not the case
for the fluoroquinolone class of antimicrobials
which are widely used in animals and for the
treatment of enteric infections in man. Until
recently, diarrhoeal infections in man were
unlikely to be treated with an antimicrobial
agent unless they were prolonged or complicated. Anecdotal evidence suggests that agents
such as ciprofloxacin are now widely prescribed
for diarrhoeal infections by general practitioners due to a perceived rapid resolution of
symptoms allowing the patient's early return to
work and a reduced loss of income. Fluoroquinolone-resistant salmonellae and campylobacter have already been isolated from
animals, foodstuffs and man (Endtz el al.,
1991; Piddock, Whale & Wise, 1990a; Piddock
ei al., 19906, Gaunt & Piddock, 1996),
although evidence showing the full sequence of
events including the compromise of antibiotic
choice by the clinician has not yet been
published. Further complications to this issue
are the sporadic reports stating that the isolates
of antibiotic-resistant organisms prevalent in
animals are different to those that cause
infection in man (e.g. Parsonnet & Kass, 1987;
Geilhausen & Mauff, 1993). Such reports have
often been used to dispel the concerns that
antibiotic-resistant zoonoses present a hazard
to human health. However, data has recently
been published to show that poultry can be a
source of vancomycin-resistant enterococci,
and that these strains can become part of the
faecal flora in man (Bates, Jordens & Griffiths,
1994). It was suggested by these authors that
emergence and nosocomial spread of vancomycin-resistant enterococci in hospital
patients may reflect antibiotic usage and
selection of these strains from such faecal flora.
The questions raised in this article require
urgent attention as clinically relevant antibiotic-resistant pathogens are increasingly
being isolated from food (Frost, Threlfall &
Rowe, 1995). Since antibiotic-resistant bacteria
that can cause human infection may be
transferred via food from animals, many
believe that antibiotics that are used in humans
should not be used in animals, and this was the
recommendation of the Swann committee in
1969 (HMSO, 1969). However, although in the
United Kingdom different drugs from an
antibiotic class are used in animals compared
with man (e.g the fluoroquinolones enrofloxacin and ciprofloxacin), bacteria are
unable to distinguish between two such
chemically similar molecules and selection of
resistance to one drug leads to cross resistance
to the other. In addition, the greater understanding of the mechanisms of multiple drug
resistance has shown that a single drug can
select resistance to several chemically unrelated
agents. Until further information is available
great caution should be exercised in the use of
antibiotics in animals and, for patients with a
foodstuff-derived infection that requires antimicrobial chemotherapy, it is prudent to
suggest that antibiotic susceptibility of the
pathogen be determined.
LAURA J V. PIDDOCK
Antimicrobial Agents Research Group.
Department of Infection.
University of Birmingham.
Birmingham BI5 ITT. UK
Tel. +44-121-414-6969; Fax +44-121-414-6966.
e-mail, l.j.v.piddockto bham ac uk
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